US2004058325A1PendingUtilityA1
Gene expression in biological conditions
Priority: Dec 29, 1999Filed: Dec 29, 2000Published: Mar 25, 2004
Est. expiryDec 29, 2019(expired)· nominal 20-yr term from priority
G01N 33/5753C12Q 1/6886G01N 2800/52C12Q 2600/112C12Q 2600/158
21
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Claims
Abstract
The invention concerns a method of determining the presence or absence of a biological condition in humans, in particular of colon cancer, and of determining the stage of a condition in human tissue by determining an expression pattern of a cell sample. Further, the invention relates to a method of determining the presence or absence of a biological condition in human tissue, and of determining the stage of a biological condition in human tissue, and also for reducing biological abnormalities of a cell suffering from the biological condition. A method for producing antibodies against an expression product of a cell from the tissue is also described. The invention also discloses a pharmaceutical composition for the treatment of a biological condition comprising at least one antibody, and a vaccine for the prophylaxis or treatment of a biological condition. Further the invention describes the use of a method for producing an assay for diagnosing a biological condition in human tissue, the use of a peptide or a gene or a probe for the preparation of a pharmaceutical composition for the treatment of a biological condition in human tissue, and an assay for determining the presence or absence of biological condition in human tissue and for determining an expression pattern of a cell.
Claims
exact text as granted — not AI-modified1 . A method of determining the presence or absence of a biological condition in animal tissue
comprising collecting a sample comprising cells from the tissue and/or expression products from the cells, assaying a first expression level of at least one gene from a first gene group, wherein the gene from the first gene group is selected from genes expressed in normal tissue cells in an amount higher than expression in biological condition cells, and assaying a second expression level of at least one gene from a second gene group, wherein the second gene group is selected from genes expressed in a normal tissue cells in an amount lower than expression in biological condition cells, correlating the first expression level to a standard expression level for normal tissue, and/or the second expression level to a standard expression level for biological condition cells to determine the presence or absence of a biological condition in the animal issue.
2 . The method of claim 1 , wherein the animal tissue is selected from epithelial tissue.
3 . The method of claim 2 , wherein the animal tissue is selected from epithelial tissue in the gastro-intestinal tract.
4 . The method of claim 3 , wherein the animal tissue is selected from epithelial tissue in colon and/or rectum.
5 . The method according to claim 4 , wherein the animal tissue is mucosa.
6 . The method of any of the preceding claims, wherein the biological condition is an adenocarcinoma, a carcinoma, a teratoma, a sarcoma, and/or a lymphoma.
7 . The method of any of the preceding claims, wherein the sample is a biopsy of the tissue.
8 . The method according to any of the preceding claim 1 - 6 , wherein the sample is a cell suspension made from the tissue.
9 . The method according to any of the preceding claims, wherein the sample comprises substantially only cells from said tissue.
10 . The method according to claim 9 , wherein the sample comprises substantially only cells from mucosa.
11 . The method according to any of the claims 3 - 10 , wherein the gene from the first gene group is selected individually from genes comprising a sequence as identified below
RC_H04768_at
chrom 15 no homology
RC_Z39652_at
Y14593 APM-1 gene adipocyte-specific
secretory protein; chrom 1q21.3-q23
RC_H30270_at
chrom 18 PAAAA in colon & bladder
no homology
RC_T47089_s_at
tenascin-X; tenascin-X precursor;
unidentified protein
RC_W31906_at
secretagogin; dJ501N12.8 (putative
protein) chrom 6
RC_AA279803_at
chrom 2 no homology
RC_R01646_at
chrom 13q32.1-33.3; AL159152;
homology to mous Pcbp1 -
poly(rC)-binding protein 1
RC_AA099820_at
BAC clone AC016778
AA319615_at
secretory carrier membrane protein;
secretory carrier membrane protein
2; chrom 15
H07011_at
tetraspan NET-6 mRNA; transmembrane
4 superfamily; chrom 7
RC_T68873_f_at
RC_T40995_f_at
RC_H81070_f_at
RC_N30796_at
RC_W37778_f_at
RC_R70212_s_at
RC_AA426330_at
RC_N33927_s_at
RC_T90190_s_at
RC_AA447145_at
RC_H75860_at
RC_T71132_s_at
wherein the notation refers to Accession No. in the database UniGene (Build 18).
12 . The method according to claim 11 , wherein the gene from the first gene group is selected individually from genes comprising a sequence as identified below
RC_H04768_at
chrom 15 no homology
RC_Z39652_at
Y14593 APM-1 gene adipocyte-specific
secretory protein; chrom 1q21.3-q23
RC_H30270_at
chrom 18 PAAAA in colon & bladder
no homology
RC_T47089_s_at
tenascin-X; tenascin-X precursor;
unidentified protein
RC_W31906_at
secretagogin; dJ501N12.8 (putative
protein) chrom 6
RC_AA279803_at
chrom 2 no homology
RC_R01646_at
chrom 13q32.1-33.3; AL159152;
homology to mouse Pcbp1 -
poly(rC)-binding protein 1
RC_AA099820_at
BAC clone AC016778
AA319615_at
secretory carrier membrane protein;
secretory carrier membrane protein
2; chrom 15
H07011_at
tetraspan NET-6 mRNA; transmembrane
4 superfamily; chrom 7
wherein the notation refers to Accession No. in the database UniGene (Build 18).
13 . The method according to claim 12 , wherein the gene from the first gene group is selected individually from genes comprising a sequence as identified below
RC H04768 at
chrom 15 no homology
RC_Z39652_at
Y14593 APM-1 gene adipocyte-specific
secretory protein; chrom 1q21.3-q23
RC_H30270_at
chrom 18 PAAAA in colon & bladder
no homology
RC_T47089_s_at
tenascin-X; tenascin-X precursor;
unidentified protein
RC_W31906_at
secretagogin; dJ501N12.8 (putative
protein) chrom 6
RC_AA279803_at
chrom 2 no homology
RC_R01646_at
chrom 13q32.1-33.3; AL159152;
homology to mouse Pcbp1 -
poly(rC)-binding protein 1
AA319615_at
secretory carrier membrane protein;
secretory carrier membrane protein
2; chrom 15
wherein the notation refers to Accession No. in the database UniGene (Build 18).
14 . The method according to claim 13 , wherein the gene from the first gene group is selected individually from genes comprising a sequence as identified below
RC_T47089_s_at
tenascin-X; tenascin-X precursor;
unidentified protein
RC_W31906_at
secretagogin; dJ501N12.8 (putative
protein) chrom 6
RC_AA279803_at
chrom 2 no homology
AA319615_at
secretory carrier membrane protein;
secretory carrier membrane protein
2; chrom 15
wherein the notation refers to Accession No. in the database UniGene (Build 18)
15 . The method according to any of claims 3 - 14 , wherein the second gene group are selected individually from genes comprising a sequence as identified below
RC_AA609013_s_at
microsomal dipeptidase (also on 6.8
k); chrom 16
RC_AA232508_at
CGI-89 protein; unnamed protein
product; hypothetical protein
RC_AA428964_at
serine protease-like protease; serine
protease homolog = NES1; normal
epithelial cell-specific 1
RC_T52813_s_at
dJ28O10.2 (G0S2 (PUTATIVE LYMPHOCYTE
G0/G1 SWITCH PROTEIN 2; chrom 1
RC_AA075642_at
gp-340 variant protein;
DMBT1/8kb.2 protein
RC_AA007218_at
chrom 13 no homology
RC_N33920_at
ubiquitin-like protein FAT10;
diubiquitin; dJ271M21.6 (Di-
ubiquitin); chrom 6
RC_N71781_at
KIAA1199 protein, chrom 15
RC_R67275_s_at
alpha-1 (type XI) collagen precursor,
collagen, type XI, alpha 1; collagen
type XI alpha-1 isoform A; chrom 1
RC_W80763_at
hypothetical protein; chrom 17
RC_AA443793_at
chrom 7p22 AC006028 BAC done
RC_AA034499_s_at
ZNF198 protein; zinc finger protein;
FIM protein; Cys-rich protein; zinc
finger protein 198; chrom 13
RC_AA035482_at
chrom 5; AK022505 done; CalcineurinB
(weakly similar)
RC_AA024482_at
hypothetical protein; unnamed protein
product; chrom 17
RC_H93021_at
chrom 2; XM_004890 peptidylprolyl
isomerase A (cyclophilin A)
RC_AA427737_at
no homology
RC_AA417078_at
chrom 7q31; AF017104 done
M29873_s_at
cytochrome P450-IIB (hIIB3);
19q13.1-q13.2
RC_H27498_f_at
RC_T92363_s_at
RC_N89910_at
RC_W60516_at
RC_AA219699_at
RC_AA449450_at
wherein the notation refers to Accession No. in the database UniGene (Build 18).
16 . The method according to any of claims 3 - 15 , wherein the second gene group are selected individually from genes comprising a sequence as identified below
RC_AA609013_s_at
microsomal dipeptidase (also on 6.8 k);
chrom 16
RC_AA232508_at
CGI-89 protein; unnamed protein product;
hypothetical protein
RC_AA428964_at
serine protease-like protease; serine
protease homolog = NES1; normal
epithelial cell-specific 1
RC_T52813_s_at
dJ28O10.2 (G0S2 (PUTATIVE
LYMPHOCYTE G0/G1 SWITCH
PROTEIN 2; chrom 1
RC_AA075642_at
gp-340 variant protein; DMBT1/8kb.2 protein
RC_AA007218_at
chrom 13 no homology
RC_N33920_at
ubiquitin-like protein FAT10; diubiquitin;
dJ271M21.6 (Diubiquitin); chrom 6
RC_N71781_at
KIAA1199 protein, chrom 15
RC_R67275_s_at
alpha-1 (type XI) collagen precursor;
collagen, type XI, alpha 1; collagen
type XI alpha-1 isoform A; chrom 1
RC_W80763_at
hypothetical protein; chrom 17
RC_AA443793_at
chrom 7p22 AC006028 BAC clone
RC_AA034499_s_at
ZNF198 protein; zinc finger protein;
FIM protein; Cys-rich protein; zinc
finger protein 198; chrom 13
RC_AA035482_at
chrom 5; AK022505 clone; CalcineurinB
(weakly similar)
RC_AA024482_at
hypothetical protein; unnamed protein
product; chrom 17
RC_H93021_at
chrom 2; XM_004890 peptidylprolyl
isomerase A (cyclophilin A)
RC_AA427737_at
no homology
RC_AA417078_at
chrom 7q31; AF017104 clone
M29873_s_at
cytochrome P450-IIB (hIIB3);
19q13.1-q13.2
wherein the notation refers to Accession No. in the database UniGene (Build 18).
17 . The method according to any of claims 3 - 14 , wherein the second gene group are selected individually from genes comprising a sequence as identified below
RC_AA609013_s_at
microsomal dipeptidase (also on 6.8 k);
chrom 16
RC_AA232508_at
CGI-89 protein; unnamed protein product;
hypothetical protein
RC_AA428964_at
serine protease-like protease; serine
protease homolog = NES1; normal
epithelial cell-specific 1
RC_AA075642_at
gp-340 variant protein; DMBT1/8kb.2 protein
RC_AA007218_at
chrom 13 no homology
RC_N33920_at
ubiquitin-like protein FAT10; diubiquitin;
dJ271M21.6 (Diubiquitin); chrom 6
RC_N71781_at
KIAA1199 protein, chrom 15
RC_R67275_s_at
alpha-1 (type XI) collagen precursor;
collagen, type XI, alpha 1; collagen
type XI alpha-1 isoform A; chrom 1
RC_W80763_at
hypothetical protein; chrom 17
RC_AA034499_s_at
ZNF198 protein; zinc finger protein; FIM
protein; Cys-rich protein; zinc finger
protein 198; chrom 13
RC_AA035482_at
chrom 5; AK022505 clone; CalcineurinB
(weakly similar)
RC_AA024482_at
hypothetical protein; unnamed protein
product; chrom 17
RC_H93021_at
chrom 2; XM_004890 peptidylprolyl isomerase
A (cyclophilin A)
RC_AA427737_at
no homology
RC_AA417078_at
chrom 7q31; AF017104 clone
M29873_s_at
cytochrome P450-IIB (hIIB3);
19q13.1-q13.2
wherein the notation refers to Accession No. in the database UniGene (Build 18).
18 . The method according to any of claims 3 - 17 , wherein the second gene group comprises a sequence as identified below
RC_W80763_at
hypothetical protein; chrom 17
wherein the notation refers to Accession No. in the database UniGene (Build 18).
19 . The method according to any of the preceding claims, wherein the expression level of at least two genes from the first gene group are determined.
20 . The method according to any of the preceding claims, wherein the expression level of at least two genes from the second gene group are determined.
21 . The method according to any of the preceding claims, further comprising the steps of determining the stage of a biological condition in the animal tissue, comprising assaying a third expression level of at least one gene from a third gene group, wherein a gene from said second gene group, in one stage, is expressed differently from a gene from said third gene group.
22 . The method according to any of the preceding claims, wherein the difference in expression level of a gene from one group to the expression level of a gene from another group is at least two-fold.
23 . The method according to any of the preceding claims, wherein the difference in expression level of a gene from one group to the expression level of a gene from another group is at least three-fold.
24 . The method according to any of the preceding claims, wherein the expression level is determined by determining the mRNA of th cells.
25 . The method according to any of the claims 1 - 23 , wherein the expression level is determined by determining expression products, such as peptides, in the cells.
26 . The method according to claim 25 , wherein the expression level is determined by determining expression products, such as peptides, in the body fluids, such as blood, serum, plasma, faeces, mucus, sputum, cerebrospinal fluid, and/or urine.
27 . A method of determining the stage of a biological condition in animal tissue,
comprising collecting a sample comprising cells from the tissue, assaying the expression of at least a first stage gene from a first stage gene group and at least a second stage gene from a second stage gene group, wherein at least one of said genes is expressed in said first stage of the condition in a higher amount than in said second stage, and the other gene is a expressed in said first stage of the condition in a lower amount than in said second stage of the condition, correlating the expression level of the assessed genes to a standard level of expression determining the stage of the condition.
28 . The method according to claim 27 , wherein the tissue is selected from the epithelial tissue in colon or rectum.
29 . The method according to any of the preceding claims 27 - 28 , wherein the difference in expression levels between a gene from one group to a gene from another group is at least one-fold.
30 . The method according to any of the preceding claims 27 - 29 , wherein the difference in expression levels between a gene from one group to a gene from another group is at least two-fold.
31 . The method according to claim 27 , wherein th stage is selected from colon cancer stag s Dukes A, Dukes B. Dukes C, and Dukes D.
32 . The method according to claim 31 , comprising assaying at least the expression of Dukes A stage gene from a Dukes A stage gene group, at least one Dukes B stage gene from a Dukes B stage gene group, at least the expression of Dukes C stage gene from a Dukes C stage gene group, and at least one Dukes D stage gene from a Dukes D stage gene group, wherein at least one gene from each gene group is expressed in a significantly different amount in that stage than in one of the other stages.
33 . The method according to claim 32 , wherein at least one gene from each gene group is expressed in a significantly higher amount in that stage than in one of the other stages.
34 . The method according to claim 33 , wherein a Dukes A stage gene is selected individually from any gene comprising a sequence as identified below
RC_AA599199_at
ALU seq.
RC_R12694_at
unnamed protein product BAA91641, chrom 10
RC_H91325_s_at
aldolase B; aldolase B (aa 1-364); chrom 9
RC_N51709_at
chrom X
RC_N72610_at
—
RC_N69263_at
chrom 10; AK026414 clone (only 108 nt hom)
RC_T15817_f_at
iNOS, inducible nitric oxide synthase
wherein the notation refers to Accession No. in the database UniGene (Build 18).
35 . The method according to claim 33 , wherein a Dukes B stage gene is selected individually from any gene comprising a sequence as identified below
RC_T67463_s_at
cathepsin O2; X; K
RC_W94688_at
perilipin
RC_AA126743_at
Z97200 PAC chrom 1q24;
PMX1 homeobox gene
RC_AA236547_at
no homology
RC_AA255567_at
angiopoi tin-related protein-2;
angiopoietin-like 2
RC_AA421256_at
—
RC_AA386386_s_at
PPPPP
—
RC_AA452549_at
PPPPP
PR01659; hypothetical protein
chrom 11
wherein the notation refers to Accession No. in the database UniGene (Build 18).
36 . The method according to claim 33 , wherein a Dukes C stage gene is selected individually from any gene comprising a sequence as identified below
RC_D45556_at
chrom 15; AL390085 clone
RC_W86214_at
RC_AA039439_s_at
novel gene KIAA0134 protein 19q13.3
RC_AA128935_at
RC_AA134158_s_at
class I homeodomain; homeobox
protein, chrom 7
RC_AA232646_at
chrom 17, AF266756 sphingosine
kinase (SPHK1
RC_AA401184_at
no homology
RC_AA436840_at
RC_AA488655_at
RC_AA181902_at
PPPPP
AC007201 on chrom 19
(only 80 nt hom)
wherein the notation refers to Accession No. in the database UniGene (Build 18).
37 . The method according to claim 33 , wherein a Dukes D stage gene is selected individually from any gene comprising a sequence as identified below
RC_N91920_at
AAAAP
chrom 16p12-p11.2; XN_007994 retinoblastoma bin-
ding protein
RC_AA621601_at
AAAAP
chrom 17 XM_009868 RAB36 ARS oncogene family
wherein the notation refers to Accession No. in the database UniGene (Build 18).
38 . The method according to claim 32 , wherein at least one gene from each gen group is expressed in a significantly lower amount in that stage than in one of the other stages.
39 . The method according to claim 38 , wherein a Dukes A stage gene is selected individually from any gene comprising a sequence as identified below
RC_N32411_f_at
PAPPP
Myc-assoclated zinc-finger protein of
human islet; chrom 16
RC_AA243858_at
PAPPP
KIAA0882 protein
RC_AA486283_at
PAPPP
ras-like protein; ras-related C3
botulinum toxin substrate; dJ20J23
RC_AA490930_at
PAPPP
chrom 18; KIAA1468 protein
RC_H54088_s_at
PPPPP
ribosomal protein L41
RC_H59052_f_at
PPPPP
fungal sterol-C5-desaturase homolog;
ORF; thymosin beta-4
RC_R49198_s_at
PPPPP
—
RC_T73572_f_at
PPPPP
ferritin L-chain; L apoferritin
RC_AA477483_at
PPPPP
no matching est
wherein the notation refers to Accession No. in the database UniGene (Build 18).
40 . The method according to claim 38 , wherein a Dukes B stage gene is selected individually from any gene comprising a sequence as identified below
RC_D59847_at
PPAPP
proSAAS; granin-like neuroendocrine peptide pre-
cursor
RC_F05038_at
PPAPP
polyamine modulated factor-1; polyamine modulated
factor 1
RC_N41059_at
PPAPP
chrom 3
RC_T23460_at
PPAPP
chrom3; IFNAR2 21q22.11
RC_W42789_at
PPAPP
chrom 8 AF268037 C8ORF4 protein (C8ORF4)
chrom 8 ORF
RC_AA460017_i_at
PPAPP
BAC clone chrom 16
RC_AA482127_at
PPAPP
KIAA1142 protein
RC_AA504806_at
PPAPP
chrom 2 AF052107 clone 23620 mRNA sequence
RC_T90037_at
PPPPP
unnamed protein product, chrom 4
RC_AA432130_at
PPPPP
KIAA0867 protein, chrom 12
wherein the notation refers to Accession No. in the database UniGene (Build 18).
41 . The method according to claim 38 , wherein a Dukes C stage gene is selected individually from any gene comprising a sequence as identified below
RC_N30231_at
PPPAP
Lsm4 protein; U6 snRNA-associated
Sm-like protein LSm4; glycine-rich
protein
RC_W73790_f_at
PPPAP
immunoglobulin-related protein 14.1;
lambda L-chain C region; omega protein,
chrom 22
RC_AA412184_at
PPPAP
chrom 1p36; d89060 dolichyl-
diphosphooligosaccharide-protein
glycosyltransferase
RC_AA521303_at
PPPAP
methionine adenosyltransferase
regulatory beta subunit;
dTDP-4-keto-6-deoxy-D-glucose
4-reductase, chrom 5
RC_AA461174_at
PPPPP
8p21.3-p22 AB020860 anti-oncogene
AA393432_s_at
PPPPP
chrom 2, Unknown; unnamed protein
product AAD20029
wherein the notation refers to Accession No. in the database UniGene (Build 18).
42 . The method according to claim 38 , wherein a Dukes D stage gene is selected individually from any gene comprising a sequence as identified below
RC_R72886_s_at
PPPPA
KIAA0422; adenylyl cyclase type VI, chrom 12
RC_AA026030_at
PPPPA
chrom 1
RC_Z39006_at
PPPPA
hypothetical protein, chrom 17
RC_AA435908_at
PPPPA
chrom 19; ac011491 clone and 20 nt hom. RAB2,
RAS oncogene family
RC_AA057829_s_at
PPPPA
growth-arrest-specific protein; growth arrest-specific
6; AXL stimulatory factor, chrom 13
RC_R72087_at
PPPPA
chrom 5 EST; hom to chrom 20 AL356652 clone
RC_H04242_at
PPPPA
ras related protein Rab5b; RAB5B, member RAS
oncogene family
RC_R97304_f_at
PPPPA
HLA-drb5; cell surface glycoprotein; MHC HLA-DR-
beta chain precursor chrom 6
RC_N48609_at
PPPPA
chrom 11; AC004584 chrom 17
RC_W86850_f_at
PPPPA
chrom 22 ? X96924 mitochondrial citrate tranbsport
region
RC_AA130603_at
PPPPA
ak024908 clone
RC_AA479610_at
PPPPA
singleton ak025344 clone
RC_AA490593_i_at
PPPPA
chrom 17 ? Synaptobrevin2 (VAMP2) AF135372
RC_AA054321_s_at
PPPPA
6p21 HLA class i region; AC004202 clone
RC_D60328_at
PPPPP
chrom 6, unknown; ring finger protein 5
RC_H96850_at
PPPPP
oligosaccharyltransferase d89060 1p36.1 (also C-
class)
RC_AA127444_at
PPPPP
chrom 1 no homology
RC_AA242824_at
PPPPP
chrom 11; ac005233 PAC clone chrom 22
AA405775_s_at
PPPPP
similar to CAA16821 (PID: g3255952)
wherein the notation refers to Accession No. in the database UniGene (Build 18).
43 . A method of determining an expression patt rn of a colon cell sample, comprising:
collecting sample comprising colon and/or rectum cells and/or expression products from colon and/or rectum cells, determining the expression level of two or more genes in the sample, wherein at least one gene belongs to a first group of genes, said gene from the first gene group being expressed in a higher amount in normal tissue than in biological condition cells, and wherein at least one other gene belongs to a second group of genes, said gene from the second gene group being expressed in a lower amount in normal tissue than in biological condition cells, and the difference between the expression level of the first gene group in normal cells and biological condition cells being at least two-fold, obtaining an expression pattern of the colon and/or rectum cell sample.
44 . The method of claim 43 , wherein the two or more genes exclude genes which are expressed in the submucosal, muscle, or connective tissue, whereby a pattern of expression is formed for the sample which is independent of the proportion of submucosal, muscle, or connective tissue cells in the sample.
45 . The method of claim 44 , comprising determining the expression level of one or more genes in the sample comprising predominantly submucosal, muscle, and connective tissue cells, obtaining a second pattern, subtracting said second pattern from the expression pattern of the colon and/or rectum cell sample, forming a third pattern of expression, said third pattern of expression reflecting expression of the colorectal mucosa or colorectal cancer cells independent of the proportion of submucosal, muscle, and connective tissue cells present in the sample.
46 . The method of any of the preceding claims 43 - 45 , wherein the sample is a biopsy of the tissue.
47 . The method according to any of the preceding claim 43 - 46 , wherein the sample is a cell suspension.
48 . The method according to any of the preceding claims 43 - 47 , wherein the sample comprises substantially only cells from said tissue.
49 . The method according to claim 48 , wherein the sample comprises substantially only cells from mucosa.
50 . The method according to any of the claims 43 - 47 , wherein the gene from the first gene group is selected individually from
RC_H04768_at
chrom 15 no homology
RC_Z39652_at
Y14593 APM-1 gene adipocyte-specific secretory
protein; chrom 1q21.3-q23
RC_H30270_at
chrom 18 PAAAA in colon & bladder no homology
RC_T47089_s_at
tenascin-X; tenascin-X precursor;
unidentified protein
RC_W31906_at
secretagogin; dJ501N12.8 (putative protein) chrom 6
RC_AA279803_at
chrom 2 no homology
RC_R01646_at
chrom 13q32.1-33.3; AL159152; homology to
mouse Pcbp1 - poly(rC)-binding protein 1
RC_AA099820_at
BAC clone AC016778
AA319615_at
secretory carrier membrane protein; secretory carrier
membrane protein 2; chrom 15
H07011_at
tetraspan NET-6 mRNA; transmembrane 4
superfamily; chrom 7
RC_T68873_f_at
RC_T40995_f_at
RC_H81070_f_at
RC_N30796_at
RC_W37778_f_at
RC_R70212_s_at
RC_AA426330_at
RC_N33927_s_at
RC_T90190_s_at
RC_AA447145_at
RC_H75860_at
RC_T71132_s_at
wherein the notation refers to Accession No. in the database UniGene (Build 18).
51 . The method according to claim 50 , wherein the gene from the first gene group is selected individually from genes comprising a sequence as identified below
RC_H04768_at
chrom 15 no homology
RC_Z39652_at
Y14593 APM-1 gene adipocyte-specific secretory
protein; chrom 1q21.3-q23
RC_H30270_at
chrom 18 PAAAA in colon & bladder no homology
RC_T47089_s_at
tenascin-X; tenascin-X precursor,
unidentified protein
RC_W31906_at
secretagogin; dJ501N12.8 (putative protein)
chrom 6
RC_AA279803_at
chrom 2 no homology
RC_R01646_at
chrom 13q32.1-33.3; AL159152; homology to
mouse Pcbp1 - poly(rC)-binding protein 1
RC_AA099820_at
BAC clone AC016778
AA319615_at
secretory carrier membrane protein; secretory
carrier membrane protein 2; chrom 15
H07011_at
tetraspan NET-6 mRNA; transmembrane 4
superfamily; chrom 7
wherein the notation refers to Accession No. in the database UniGene (Build 18).
52 . The method according to claim 51 , wherein the gene from the first gene group is selected individually from genes comprising a sequence as identified below
RC_H04768_at
chrom 15 no homology
RC_Z39652_at
Y14593 APM-1 gene adipocyte-specific secretory
protein; chrom 1q21.3-q23
RC_H30270_at
chrom 18 PAAAA in colon & bladder no homology
RC_T47089_s_at
tenascin-X; tenascin-X precursor;
unidentified protein
RC_W31906_at
secretagogin; dJ501N12.8 (putative protein)
chrom 6
RC_AA279803_at
chrom 2 no homology
RC_R01646_at
chrom 13q32.1-33.3; AL159152; homology to
mouse Pcbp1 - poly(rC)-binding protein 1
AA319615_at
secretory carrier membrane protein; secretory
carrier membrane protein 2; chrom 15
wherein the notation refers to Accession No. in the database UniGene (Build 18).
53 . The method according to claim 52 , wherein the gene from the first gene group is selected individually from genes comprising a sequence as identified below
RC_T47089_s_at
tenascin-X; tenascin-X precursor
unidentified protein
RC_W31906_at
secretagogin; dJ501N12.8 (putative protein) chrom 6
RC_AA279803_at
chrom 2 no homology
AA319615_at
secretory carrier membrane protein; secretory
carrier membrane protein 2; chrom 15
wherein the notation refers to Accession No. in the database UniGene (Build 18).
54 . The method according to any of claims 3 - 14 , wherein the second gene group are selected individually from genes comprising a sequence as identified below
RC_AA609013_s_at
microsomal dipeptidase (also on 6.8 k);
chrom 16
RC_AA232508_at
CGI-89 protein; unnamed protein product
hypothetical protein
RC_AA428964_at
serine protease-like protease; serine
protease homolog = NES1; normal
epithelial cell-specific 1
RC_T52813_s_at
dJ28O10.2 (G0S2 (PUTATIVE LYMPHOCYTE
G0/G1 SWITCH PROTEIN 2; chrom 1
RC_AA075642_at
gp-340 variant protein; DMBT1/8kb.2
protein
RC_AA007218_at
chrom 13 no homology
RC_N33920_at
ubiquitin-like protein FAT10;
diubiquitin; dJ271M21.6 (Diubiquitin);
chrom 6
RC_N71781_at
KIAA1199 protein, chrom 15
RC_R67275_s_at
alpha-1 (type XI) collagen precursor,
collagen, type XI, alpha 1; collagen
type XI alpha-1 Isoform A; chrom 1
RC_W80763_at
hypothetical protein; chrom 17
RC_AA443793_at
chrom 7p22 AC006028 BAC clone
RC_AA034499_s_at
ZNF198 protein; zinc finger protein;
FIM protein; Cys-rich protein; zinc
finger protein 198; chrom 13
RC_AA035482_at
chrom 5; AK022505 clone; CalcineurinB
(weakly similar)
RC_AA024482_at
hypothetical protein; unnamed protein
product; chrom 17
RC_H93021_at
chrom 2; XM_004890 p ptidylprolyl
isomerase A (cyclophilin A)
RC_AA427737_at
no homology
RC_AA417078_at
chrom 7q31; AF017104 clone
M29873_s_at
cytochrome P450-IIB (hIIB3);
19q13.1-q13.2
RC_H27498_f_at
RC_T92363_s_at
RC_N89910_at
RC_W60516_at
RC_AA219699_at
RC_AA449450_at
wherein the notation refers to Accession No. in the database UniGene (Build 18).
55 . The method according to any of claims 43 - 49 , wherein the second gene group are selected individually from genes comprising a sequence as identified below
RC_AA609013_s_at
microsomal dipeptidase (also on 6.8 k);
chrom 16
RC_AA232508_at
CGI-89 protein; unnamed protein product;
hypothetical protein
RC_AA428964_at
serine protease-like protease; serine
protease homolog = NES1; normal
epithelial cell-specific 1
RC_T52813_s_at
dJ28O10.2 (G0S2 (PUTATIVE LYMPHOCYTE
G0/G1 SWITCH PROTEIN 2; chrom 1
RC_AA075642_at
gp-340 variant protein; DMBT1/8kb.2
protein
RC_AA007218_at
chrom 13 no homology
RC_N33920_at
ubiquitin-like protein FAT10;
diubiquitin; dJ271M21.6 (Diubiquitin);
chrom 6
RC_N71781_at
KIAA1199 protein, chrom 15
RC_R67275_s_at
alpha-1 (type XI) collagen precursor;
collagen, type XI, alpha 1; collagen
type XI alpha-1 isoform A; chrom 1
RC_W80763_at
hypothetical protein; chrom 17
RC_AA443793_at
Chrom 7p22 AC006028 BAC clone
RC_AA034499_s_at
ZNF198 protein; zinc finger protein;
FIM protein; Cys-rich protein; zinc
finger protein 198; chrom 13
RC_AA035482_at
chrom 5; AK022505 clone; CalcineurinB
(weakly similar)
RC_AA024482_at
hypothetical protein; unnamed prot in
product; chrom 17
RC_H93021_at
chrom 2; XM_004890 peptidylprolyl
isomerase A (cyclophilin A)
RC_AA427737_at
no homology
RC_AA417078_at
chrom 7q31; AF017104 clone
M29873_s_at
cytochrome P450-IIB (hIIB3);
19q13.1-q13.2
wherein the notation refers to Accession No. in the database UniGene (Build 18).
56 . The method according to any of claims 43 - 49 , wherein the second gene group are selected individually from genes comprising a sequence as identified below
RC_AA609013_s_at
microsomal dipeptidase (also on 6.8 k);
chrom 16
RC_AA232508_at
CGI-89 protein; unnamed protein product;
hypothetical protein
RC_AA428964_at
serine protease-like protease; serine
protease homolog = NES1; normal
epithelial cell-specific 1
RC_AA075642_at
gp-340 variant protein; DMBT1/8kb.2 protein
RC_AA007218_at
chrom 13 no homology
RC_N33920_at
ubiquitin-like protein FAT10; diubiquitin;
dJ271M21.6 (Diubiquitin); chrom 6
RC_N71781_at
KIAA1199 protein, chrom 15
RC_R67275_s_at
alpha-1 (type XI) collagen precursor;
collagen, type XI, alpha 1; collagen type XI
alpha-1 isoform A; chrom 1
RC_W80763_at
hypothetical protein; chrom 17
RC_AA034499_s_at
ZNF198 protein; zinc finger protein;
FIM protein; Cys-rich protein; zinc finger
protein 198; chrom 13
RC_AA035482_at
chrom 5; AK022505 clone; CalcineurinB
(weakly similar)
RC_AA024482_at
hypothetical protein; unnamed protein
product; chrom 17
RC_H93021_at
chrom 2; XM_004890 peptidylprolyl
Isomerase A (cyclophilin A)
RC_AA427737_at
no homology
RC_AA417078_at
chrom 7q31; AF017104 clone
M29873_s_at
cytochrome P450-IIB (hIIB3);
19q13.1-q13.2
wherein the notation refers to Accession No. in the database UniGene (Build 18).
57 . The method according to any of claims 43 - 49 , wherein the second gene group comprises a sequence as identified below
RC_W80763_at
Hypothetical protein; chrom 17
the notation refers to Accession No in the database UniGene (Build 18).
58 . The method according to any of the preceding claims 43 - 57 , wherein the expression level of at least two genes from the first gene group are determined.
59 . The method according to any of the preceding claims 43 - 58 , wherein the expression level of at least two genes from the second gene group are determined.
60 . A method of determining an expression pattern of a colon cell sample independent of the proportion of submucosal, muscle, or connective tissue cells present, comprising:
determining the expression of one or more genes in a sample comprising cells, wherein the one or more genes exclude genes which are expressed in the submucosal, muscle, or connective tissue, whereby a pattern of expression is formed for the sample which is independent of the proportion of submucosal, muscle, or connective tissue cells in the sample.
61 . The method according to claim 60 , comprising determining the expression level of one or more genes in the sample comprising predominantly submucosal, muscle, and connective tissue cells, obtaining a second pattern, subtracting said second pattern from the expression pattern of the colon and/or rectum cell sample, forming a third pattern of expression, said third pattern of expression reflecting xpression of the colon cells independent of th proportion of submucosal, muscle, and connective tissue cells present in the sample.
62 . A method of determining the presence or absence of a biological condition in human colon and/or rectum tissue comprising,
collecting a sample comprising cells from the tissue, determining an expression pattern of the cells as defined in any of claims 43 - 61 , correlating the determined expression pattern to a standard pattern, determining the presence or absence of the biological condition of said tissue.
63 . A method for determining the stage of a biological condition in animal tissue, comprising
collecting a sample comprising cells from the tissue, determining an expression pattern of the cells as defined in any of claims 43 - 61 , correlating the determined expression pattern to a standard pattern, determining the stage of the biological condition is said tissue.
64 . A method for reducing cell tumorigenicity of a cell, said method comprising
contacting a tumor cell with at least one peptide expressed by at least one gene selected from genes being expressed in an at least two-fold higher in normal cells than the amount expressed in said tumor cell.
65 . The method according to claim 64 , wherein the at least one gene is selected individually from genes comprising a sequence as identified below
RC_H04768_at
chrom 15 no homology
RC_Z39652_at
Y14593 APM-1 gene adipocyte-specific secretory
protein; chrom 1q21.3-q23
RC_H30270_at
chrom 18 PAAAA in colon & bladder no homology
RC_T47089_s_at
tenascin-X; tenascin-X precursor; unidenti-
fied protein
RC_W31906_at
secretagogin; dJ501N12.8 (putative protein)
chrom 6
RC_AA279803_at
chrom 2 no homology
RC_R01646_at
chrom 13q32.1-33.3; AL159152; homology to
mouse Pcbp1 - poly(rC)-binding protein 1
AA319615_at
secretory carrier membrane protein; secretory
carrier membrane protein 2; chrom 15
wherein the notation refers to Accession No. in the database UniGene (Build 18).
66 . The method according to claim 64 or 65 , wherein the tumor cell is contacted with at least two different peptides.
67 . A method for reducing cell tumorigenicity of a cell, said method comprising
obtaining at least one gene selected from genes being expressed in an at least twofold higher in normal cells than the amount expressed in said tumor cell, introducing said at least one gene into the tumor cell in a manner allowing expression of said gene(s).
68 . The method according to claim 67 , where the at least one gene is selected individually from genes comprising a sequence as identified below
RC_H04768_at
chrom 15 no homology
RC_Z39652_at
Y14593 APM-1 gene adipocyte-specific secretory
protein; chrom 1q21.3-q23
RC_H30270_at
chrom 18 PAAAA in colon & bladder no homology
RC_T47089_s_at
tenascin-X; tenascin-X precursor; unidentified
protein
RC_W31906_at
secretagogin; dJ501N12.8 (putative protein)
chrom 6
RC_AA279803_at
chrom 2 no homology
RC_R01646_at
chrom 13q32.1-33.3; AL159152; homology to
mouse Pcbp1 - poly(rC)-binding protein 1
AA319615_at
secretory carrier membrane protein; secretory
carrier membrane protein 2; chrom 15
wherein the notation refers to Accession No. in the database UniGene (Build 18).
69 . The method according to claim 67 or 68 , wherein at least two different genes are introduced into the tumor cell.
70 . A method for reducing cell tumorigenicity of a cell, said method comprising
obtaining at least one nucleotide probe capable of hybridising with at least one gene of a tumor cell, said at least one gene being selected from genes being expressed in an amount at least one-fold lower in normal cells than the amount expressed in said tumor cell, and introducing said at least one nucleotide probe into the tumor cell in a manner allowing the probe to hybridise to the at least one gene, thereby inhibiting expression of said at least one gene.
71 . The method according to claim 70 , wherein the nucleotide probe is selected from probes capable of hybridising to a nucleotide sequence comprising a sequence as identified below
RC_AA609013_s_at
APPPP
microsomal dipeptidase (also
on 6.8 k); chrom 16
RC_AA232508_at
APPPP
CGI-89 protein; unnamed protein
product; hypothetical protein
RC_AA428964_at
APPPP
serine protease-like protease;
serine protease homolog =
NES1; normal epithelial cell-
specific 1
RC_T52813_s_at
APPPP
dJ28O10.2 (G0S2 (PUTATIVE
LYMPHOCYTE G0/G1 SWITCH
PROTEIN 2; chrom 1
RC_AA075642_at
APPPP
gp-340 variant protein;
DMBT1/8kb.2 protein
RC_AA007218_at
APPPP
chrom 13 no homology
RC_N33920_at
APPPP
ubiquitin-like protein FAT10;
diubiquitin; dJ271M21.6
(Diubiquitin); chrom 6
RC_N71781_at
APPPP
KIAA1199 protein, chrom 15
RC_R67275_s_at
APPPP
alpha-1 (type XI) collagen
precursor; collagen, type
XI, alpha 1; collagen type
XI alpha-1 isoform A;
chrom 1
RC_W80763_at
APPPP
hypothetical protein; chrom 17
RC_AA443793_at
APPPP
chrom 7p22 AC006028 BAC clone
RC_AA034499_s_at
APPPP
ZNF198 protein; zinc finger
protein; FIM protein;
Cys-rich protein; zinc finger
protein 198; chrom 13
RC_AA035482_at
APPPP
chrom 5; AK022505 clone;
CalcineurinB (weakly
similar)
RC_AA024482_at
APPPP
hypothetical protein; unnamed
protein product; chrom 17
RC_H93021_at
APPPP
chrom 2; XM_004890 peptidyl-
prolyl isomerase A
(cyclophilin A)
RC_AA427737_at
APPPP
no homology
RC_AA417078_at
APPPP
chrom 7q31; AF017104 clone
M29873_s_at
APPPP
cytochrome P450-IIB (hIIB3);
19q13.1-q13.2
RC_H27498_f_at
AAPPP
RC_T92363_s_at
AAPPP
RC_N89910_at
AAAPP
RC_W60516_at
AAAPP
RC_AA219699_at
AAAPP
RC_AA449450_at
AAAPP
wherein the notation refers to Accession No. in the database UniGene (Build 18).
72 . The method according to claim 70 or 71 , wherein at least two different genes ar introduced into the tumor cell.
73 . A method for producing antibodies against an expression product of a cell from a biological tissue, said method comprising the steps of
obtaining expression product(s) from at least one gene said gene being expressed as defined in any of claims 27 - 37 , immunising a mammal with said expression product(s) obtaining antibodies against the expression product.
74 . A pharmaceutical composition for the treatment of a biological condition comprising at least one antibody produced as described in claim 73 .
75 . A vaccine for the prophylaxis or treatment of a biological condition comprising at least one expression product from at least one gene said gene being expressed as defined in any of claims 27 - 37 .
76 . The use of a method as defined in any of claims 1 - 63 for producing an assay for diagnosing a biological condition in animal tissue.
77 . The use of a peptide as defined in any of claims 64 - 66 for preparation of a pharmaceutical composition for the treatment of a biological condition in animal tissue.
78 . The use of a gene as defined in any of claims 67 - 69 for preparation of a pharmaceutical composition for the treatment of a biological condition in animal tissue.
79 . The use of a probe as defined in any of claims 70 - 72 for preparation of a pharmaceutical composition for the treatment of a biological condition in animal tissue.
80 . An assay for determining the presence or absence of a biological condition in animal tissue, comprising
at least one first marker capable of detecting a first expression level of at least one gene from a first gene group, wherein the gene from the first gene group is selected from genes expressed in normal tissue cells in an amount higher than expression in biological condition cells, at least one second marker capable of detecting a second expression level of at least one gene from a second gene group, wherein the second g ne group is selected from genes expressed in normal tissue cells in an amount lower than expression in biological condition cells.
81 . The assay according to claim 80 , wherein the marker is a nucleotide probe.
82 . The assay according to claim 80 , wherein the marker is an antibody.
83 . The assay according to claim 80 , wherein the genes are as defined in any of claims 11 - 18 , 34 - 37 , and 39 - 42 .
84 . An assay for determining an expression pattern of a colon and/or rectum cell, comprising at least a first marker and a second marker, wherein the first marker is capable of detecting a gene from a first gene group as defined in claim 43 , and the second marker is capable of detecting a gene from a second gene group as defined in claim 43 .
85 . The assay according to claim 84 , wherein the first marker is capable of detecting one gene as identified in Table I, and the second marker is capable of detecting another gene as identified in Table I.
86 . The assay according to claim 85 , comprising at least two markers for each gene group,
correlating the first expression level and the second expression level to a standard level of the assessed genes to determine the presence or absence of a biological condition in the animal tissue.
87 . The assay according to claim 86 , wherein the marker is a nucleotide probe
88 . The assay according to claim 86 , wherein the marker is an antibody.
89 . A method for identifying a tissue sample as colorectal, comprising subjecting the tissue to a method as identified in any of claims 43 - 51 , determining expression patterns and comparing the expression patterns determin d with expression patterns from colo-rectal tissue.Join the waitlist — get patent alerts
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